EP0006724A1 - Harnstoff enthaltende pharmazeutische Zusammensetzungen - Google Patents

Harnstoff enthaltende pharmazeutische Zusammensetzungen Download PDF

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Publication number
EP0006724A1
EP0006724A1 EP79301159A EP79301159A EP0006724A1 EP 0006724 A1 EP0006724 A1 EP 0006724A1 EP 79301159 A EP79301159 A EP 79301159A EP 79301159 A EP79301159 A EP 79301159A EP 0006724 A1 EP0006724 A1 EP 0006724A1
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EP
European Patent Office
Prior art keywords
component
composition
weight
medicament
urea
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP79301159A
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English (en)
French (fr)
Other versions
EP0006724B1 (de
Inventor
Steven Leigh
Peter James Ayres
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Phares Pharmaceutical Research NV
Original Assignee
PHARES PHARMA RES NV
Phares Pharmaceutical Research NV
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
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Application filed by PHARES PHARMA RES NV, Phares Pharmaceutical Research NV filed Critical PHARES PHARMA RES NV
Publication of EP0006724A1 publication Critical patent/EP0006724A1/de
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Publication of EP0006724B1 publication Critical patent/EP0006724B1/de
Expired legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S424/00—Drug, bio-affecting and body treating compositions
    • Y10S424/15—Suppositories

Definitions

  • This invention relates to pharmaceutical compositions containing urea.
  • compositions containing medicaments which are sensitive to water There exist many medicaments, of which tetracycline is an example, which can readily be administered topically, but which are not formulated for topical application because of the short shelf life of the formulations due to the deliberate or accidental presence of small proportions of water.
  • Urea is well known as an agent for the treatment of hyper-keratotic conditions of the skin.
  • urea can also act as a hydrating agent by becoming bound to water molecules. In particular, it is capable of hydrating the skin so as to allow the percutaneous transportation of medication, thus acting as a drug delivery system.
  • urea potentiates the action of a wide range of drugs.
  • the use of urea in compositions for topical application has been, however, severely restricted by the fact that urea is unstable in neutral aqueous solution and tends to decompose with the liberation of carbon dioxide and ammonia.
  • One solution to this problem described in British Patent Specification No. 1,468,815, has been to provide the urea in the form of an aqueous solution adsorbed on particles of a water-soluble powder such as starch which are themselves dispersed in a continuous hydrophobic phase.
  • Urea is a coarsely crystalline material, and the solid needs to be micronized before incorporation if the resulting composition is not to have a gritty texture. But in the presence of water, even micronized urea rapidly undergoes crystal growth and develops a gritty texture.
  • the invention provides a pharmaceutical composition comprising:-
  • component a) in the above definition is preferably:-
  • the medicament is provided in the form of small solid particles preferably having a particle size in the range from 0.1 to 60 microns.
  • the medicament is dispersed in a melt of the waxy material which is then sprayed conveniently by conventional means such as a standard air spray gun, an airless spray gun or by ultrasonic atomization.
  • the spraying preferably takes place within an enclosed chamber where the particles of sprayed suspension congeal to form sphereswith the finely divided drug enclosed within the spheres.
  • the average diameter of the spheres preferably falls within the range from 2 to 80 microns, particularly from 10 to 60 microns.
  • the spheres may be used in a wide range of diameters, or if required graded by sieving into a narrow range.
  • the waxy material needs to be one in which the medicament is not soluble.
  • a polar medicament such as tetracycline hydrochloride
  • a hydrocarbon wax may be used;
  • a non-polar medicament such as cortisol
  • a suitable grade of polyethylene glycol or a vegetable or other wax may be preferred. Since the wax spheres need to be incorporated in a melt of component d), the wax must have a higher melting point than d); preferably, the wax melts at a temperature above 37°C.
  • the stability of the medicament in the composi-' tion depends to some extent on the proportion of the medicament in the waxy particles of component a).
  • a satisfactory proportion of medicament in these particles is from 1% to 30%, particularly 4% to 12% by weight. It has been found particularly advantageous to atomise the waxy material containing the medicament above a stirred reservoir of components b), c) and d), so that the waxy particles congeal and are immediately dispersed in the remainder of the composition in a single step.
  • urea forms crystalline inclusion compounds with many straight-chain organic compounds having more than 4 carbon atoms, for example hydrocarbons, alcohols, mercaptans, alkylhalides, ketones, acids and esters, but not with branched-chain or cyclic compounds. It appears that the straight-chain compounds are bound to the urea molecules by nothing more than adsorption forces at the solid surface. The chains merely occupy channels in the urea crystal lattice. The melting point of each compound approximates to that of the urea, and the heat of formation is even less than the usual heats of adsorption on solid surfaces.
  • each compound is a definite composition
  • the ratio of urea molecules to straight-chain molecules is not stoichiometric but is proportional to the number of carbon atoms in the chain. Approximately two-thirds of a molecule of urea is combined for each angstrom of chain length.
  • inclusion compounds have been used on a commercial scale for many purposes, to improve the octane number of petrol, to lower the freezing point of fuel for jet aircraft and to lower the pour point of lubricating oil by removing the normal hydrocarbons, to isolate and purify compounds and to resolve alkylhalides into optically active components. So far as is known, such inclusion compounds have not been used in pharmaceutical compositions for topical application, and in this area they have two important advantages. They provide some protection against hydrolysis of urea by small proportions of water that may be present, either deliberately or unavoidably, in the composition.
  • the straight-chain organic compound must be one which is non-toxic and inert to the components (other than urea) of the composition.
  • straight-chain alcohols and, more particularly, carboxylic acids we prefer to use straight-chain fatty acids having from 12 to 18 carbon atoms per molecule such as lauric, palmitic and stearic acids.
  • the use of an acid has the added advantage that the carboxylic acid groups mop up any ammonia which may nevertheless be formed by hydrolysis of the urea.
  • the inclusion compounds are easily formed.
  • the urea may be partly dissolved in a water or alcohol solvent and added to a melt of the fatty acid or other organic compound.
  • the organic compound may be used in solution, e.g. in alcohol.
  • the solid urea may be added direct to a melt of the straight-chain organic compound.
  • the inclusion compound separates as a precipitate of fine particle size.
  • the nature and amount of solvent used can determine to some extent the size of the crystalline particles of inclusion compounds that are formed.
  • the proportions of the components for this reaction are not very critical; the use of quite a small amount of fatty acid helps to stabilise the urea and reduce the crystal size; the presence of an excess of fatty acid is not harmful in the composition; the solvent may be arranged to evaporate off during or after the reaction or to remain in the crystalline compound.
  • a reaction medium containing from 20% to 80%, particularly from 40% to 75%, by weight of urea, from 8% to 75%, particularly from 20% to 40%, by weight of fatty acid or other straight-chain organic compound, and from 0% to 40% by weight of solvent.
  • a water-insoluble powder is preferably included in the pharmaceutical composition of this invention.
  • the powder helps to mitigate the greasy texture of the composition, and can also assist in ensuring percutaneous absorption of the medicament.
  • the water-insoluble powder is chosen to be inert to the hydrophobic medium and to the medicament, and may be one of the wide range of powders that is conventionally used in pharmaceutical preparations, for example:
  • the average particle size of the powder should be from 1 micron to 60 microns. While this range is not critical, powders above 30 microns, and more particularly above 60 microns, tend to impart a coarse texture to pharmaceutical compositions, while powders in the sub-micron range are approaching colloidal size and are liable to affect the physical properties of the medium.
  • the carrier material is chosen to be one which does not dissolve or react with any of components a), b) or c).
  • component a) comprises a hydrocarbon wax
  • the carrier material may be, for example, an oil of vegetable origin, silicone oil or an ester such as di-isopropyl adipate or isopropyl myristate.
  • component a) is a polyethylene glycol
  • the carrier material may advantageously be a hydrocarbon such as liquid parafin or white soft parafin.
  • Thickeners for example colloidal silica, bees wax and micro-crystalline wax, may be used as desired.
  • component d) should have a softening point of not more than 37°C.
  • component d) may conveniently have a softening point of about 37°C.
  • a preferred carrier is a blend of glyceryl tribehenate, di-isopropyl adipate and purcellin oil (itself a mixture of cetyl and stearyl octanoates), in proportions to provide the desired viscosity softening point and temperature characteristics. Suitable proportions are glyceryl tribehenate 5 to 20%; di-isopropyl adipate 10 to 40%; and purcellin oil 50 to 85%.
  • a preferred composition comprises 5 to 15% by weight of component a) (itself containing 4 to 12% by weight of a dispersed medicament), from 10 to 25% by weight of component b), from 10 to 30% by weight of component c) and from 50 to 70% by weight of component d).
  • water is preferably absent, such compositions may tolerate, depending on the medicament used, up to 6% by weight of water. At all events, the amount that can be tolerated without unduly rapid decomposition of the medicament is greater than would be the case if the medicament were not protected by the spray congealing technique.
  • the nature of the medicament is not critical, and any medicament may be used which is capable of topical application.
  • the invention is of particular advantage, however, in respect of medicaments which are sensitive to water. Examples are:-
  • Sun screening preparations comprising mixtures of Vitamins A and D, generally in an amount of from 50,000 to 5,000,000 i.e. per gram.
  • compositions of this invention may be prepared simply by dispersing components a), b) and c) in a melt of component d). Obviously, the temperature of the melt must be below the melting point of component a). Dispersion may be effected by gentle stirring, to avoid disruption of the waxy particles of component a).
  • compositions of this invention are intended to be applied topically, or by means of a suppository, preferably though not necessarily to skin which is moist.
  • Water present in or on the skin dissolves the urea and provides a concentrated solution of high osmotic pressure which draws more water through the skin and generally hydrates the skin.
  • the water-insoluble powder serves two purposes. The particles disrupt the waxy spheres when the composition is rubbed into the skin, thus facilitating rapid release of the medicament. The particles also adsorb the concentrated aqueous solution of urea and maintain it in close contact with the stratum corneum.
  • the urea assists solubilization of the medicament, assists its percutaneous transportation, and may in some cases act synergystically and thus potentiate its effect.
  • Urea (10 parts) is partially dissolved in a mixture of alcohol (4 parts) and water (2 parts) at about 65 0 C and added to stearic acid (4 parts) which has been previously melted at 70 0 C.
  • the melt is maintained at 62 0 C. with continuous stirring.
  • An inclusion compound is formed and precipitates.
  • the final weight on cooling to room temperature indicates that 3 parts of the solvent has been lost by evaporation.
  • the inclusion compound formed has a smooth feathery texture and microscopically the particles are mainly between 15 and 30 microns across.
  • Wax spheres (10% tetracycline
  • Tetracycline hydrochloride is micronized to a particle size in the range 1 to 60 microns, and is suspended uniformly in a 10% by weight concentration in molten paraffin wax having a melting point of 65°C.
  • the uniform suspension is sprayed by means of a standard air spray gun and the resulting congealed spheres containing the finely divided tetracycline hydrochloride are then incorporated into a proportion of the di-isopropyl adipate.
  • the starch ether is then added and dispersed.
  • the urea adduct is dispersed, along with the colloidal silica, in the remainder of the di-isopropyl adipate.
  • the two materials are then mixed with gentle stirring to produce the final composition.
  • Cortisol is used either as the free alcohol or as a 17a-hydroxy ester, in a micronized form having a particle size in the range 1 to 60 microns.
  • This material is uniformly suspended in a water-soluble wax, specifically a polyethylene glycol of molecular weight around 4,000.
  • the suspension is then sprayed in a conventional manner and recovered in the form of spheres having an average particle size of 45 to 60 microns. These are dispersed in a proportion of the isopropyl myristate, and the starch ether added.
  • the urea adduct and surfactant are dispersed in the remainder of the isopropyl myristate and the two components mixed to form the final composition.
  • the tetracycline is vacuum dried to constant weight, and micronised in dry air to a particle size of 1-3 microns (80%).
  • the paraffin wax is heated to 80°C and the micronised tetracycline dispersed in the melted wax. (Degradation of the tetracycline to anhydro- or epi-anhydro-tetracycline was not observed to occur under these conditions.) Uniform dispersion of the tetracycline is maintained by high speed stirring of the suspension prior to and during atomisation.
  • the surfactant is added to the lipophilic medium.
  • the urea adduct is evenly dispersed in a portion of the lipophilic medium with high speed mixing.
  • the rice starch ether powder is evenly dispersed in the remainder of the lipophilic medium and this is then uniformly mixed with the urea adduct dispersion.
  • the blend is cooled to 18 0 C and stirring maintained during the formation of tetracycline microspheres.
  • Atomisation of the tetracycline suspension is effected by means of an ultrasonic velocity transformer.
  • the droplets congeal and fall into the stirred blend of the remaining components where they are rapidly dispersed to form the final composition.
  • no special drying operations are performed, and no special steps taken to prevent ingress of moisture.
  • the tetracycline in this example can be replaced by erythromycin or clindamycin.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Nanotechnology (AREA)
  • Dermatology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Medical Informatics (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Medicinal Preparation (AREA)
EP79301159A 1978-06-16 1979-06-15 Harnstoff enthaltende pharmazeutische Zusammensetzungen Expired EP0006724B1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB7827115 1978-06-16
GB2711578 1978-06-16

Publications (2)

Publication Number Publication Date
EP0006724A1 true EP0006724A1 (de) 1980-01-09
EP0006724B1 EP0006724B1 (de) 1982-12-01

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EP79301159A Expired EP0006724B1 (de) 1978-06-16 1979-06-15 Harnstoff enthaltende pharmazeutische Zusammensetzungen

Country Status (7)

Country Link
US (2) US4291062A (de)
EP (1) EP0006724B1 (de)
JP (1) JPS557272A (de)
AU (1) AU521982B2 (de)
CA (1) CA1114744A (de)
DE (1) DE2964135D1 (de)
IE (1) IE48761B1 (de)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2496460A1 (fr) * 1980-12-19 1982-06-25 Chinoin Gyogyszer Es Vegyeszet Suppositoires stables malgre un composant actif volatil et/ou decomposable et procede pour leur preparation
GB2126086A (en) * 1982-08-24 1984-03-21 Cilag Ag Medicated suppository containing gel-forming and gel-dispersing agents
GB2142238A (en) * 1983-07-01 1985-01-16 Nitto Electric Ind Co Pharmaceutical compositions for percutaneous administration
GB2142237A (en) * 1983-07-01 1985-01-16 Nitto Electric Ind Co Pharmaceutical compositions for percutaneous administration
FR2562798A1 (fr) * 1984-04-11 1985-10-18 Roehm Pharma Gmbh Agent pharmaceutique pour le traitement du psoriasis
FR2596991A1 (fr) * 1986-04-11 1987-10-16 Roehm Pharma Gmbh Medicament sous forme liquide pour le traitement du psoriasis, a base de polymeres filmogenes
EP0322197A1 (de) * 1987-12-22 1989-06-28 Drythanol Ltd. Dithranolzusammensetzungen
FR2649608A1 (fr) * 1989-07-12 1991-01-18 Oreal Composition cosmetique sous forme d'un gel aqueux contenant en suspension des spheroides d'une substance lipidique solide non hydrophile
US5674504A (en) * 1989-07-12 1997-10-07 L'oreal Cosmetic composition in the form of an aqueous gel containing in suspension spheroids of a non-hydrophilic, lipoidal substance
EP1205218A1 (de) * 2000-11-14 2002-05-15 Benkert, Eugen Georg, Dr.med.dent. Topical-Antipsoriaticum mit Harnstoff, einem Corticoid und einem Desinfektionsmittel

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4698359A (en) * 1982-08-24 1987-10-06 Cilag, Ag Medicated suppository
US4518583A (en) * 1983-02-22 1985-05-21 Gallina Damian J Hemorrhoid and anorectal disease treatment method
US4514384A (en) * 1983-03-14 1985-04-30 Gallina Damian J Hemorrhoid treatment method
EP0145711A1 (de) * 1983-06-10 1985-06-26 International Copper Association, Inc. Kupferkomplex zum behandeln von krebs
US4672078A (en) * 1985-07-03 1987-06-09 Schering-Plough Corporation Urea stabilized with a lactone in various pharmaceutical and cosmetic preparations
DE3603859A1 (de) * 1986-02-07 1987-08-13 Roehm Pharma Gmbh Abwaschbare topische zubereitung zur therapie der psoriasis
USH672H (en) 1986-12-31 1989-09-05 E. R. Squibb & Sons, Inc. Stable antifungal capsule formulation
CA2116621C (en) * 1993-03-03 2001-07-24 Rene C. Gaudreault Novel anticancer agents
TW404844B (en) * 1993-04-08 2000-09-11 Oxford Biosciences Ltd Needleless syringe
US5750547A (en) * 1995-01-06 1998-05-12 Universite Laval Certain carbanate anti-cancer agents
EP1214931A1 (de) * 2000-12-15 2002-06-19 Schering Aktiengesellschaft Mikronisierter Harnstoff enthaltende wasserfreie Hautpflegezusammensetzung und Verfahren zur Herstellung
WO2006024138A1 (en) * 2004-08-30 2006-03-09 Taro Pharmaceutical Industries Ltd. A thermoreversible pharmaceutical formulation for anti-microbial agents comprising poloxamer polymers and hydroxy fatty acid ester of polyethylene glycol
DE102005045989A1 (de) * 2005-09-27 2007-03-29 Koko Kosmetikvertrieb Gmbh & Co. Kg Universelle Pudergundlage
DE102008006791B4 (de) * 2008-01-30 2011-11-24 Lts Lohmann Therapie-Systeme Ag Transdermales Therapeutisches System mit Harnstoff-Komponente und Verfahren zu dessen Herstellung
US20140350106A1 (en) * 2013-05-22 2014-11-27 Professional Compounding Centers Of America Urea Silicone Gel for Scars and Hydration Treatment and Method of Using Same
US20140348873A1 (en) * 2013-05-22 2014-11-27 Professional Compounding Centers Of America Urea-Silicone Gel for Hyperkeratosis Treatment
RU2730852C2 (ru) * 2018-10-08 2020-08-26 Лариса Викторовна Фортунская Композиция ингредиентов для лечения грибковых кожных заболеваний стоп и ногтей (варианты)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB804492A (en) * 1955-04-25 1958-11-19 Martin Ruben Aminopyrine, caffeine or quinine hydrochloride inclusion compounds
GB1404583A (en) * 1971-10-08 1975-09-03 Vymatt Sa Urea compositions and methods of preparation thereof

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1411432A (en) * 1972-01-10 1975-10-22 Medisan Ab Skin treating compositions
JPS5210424A (en) * 1975-07-09 1977-01-26 Taisho Pharmaceut Co Ltd A method for preparing a remedy against cutaneous fungi

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB804492A (en) * 1955-04-25 1958-11-19 Martin Ruben Aminopyrine, caffeine or quinine hydrochloride inclusion compounds
GB1404583A (en) * 1971-10-08 1975-09-03 Vymatt Sa Urea compositions and methods of preparation thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CHEMICAl ABSTRACTS, Vol. 89, No. 16, 10/78. Abstract 135770j. Columbus, Ohio, USA H. MATSUMURA et al.: "Product precipitated from urea ointment and inhibition of its formation", page 396, column 1, & Yakazaigaku, 31 (2) 1977, 57-63. *

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2496460A1 (fr) * 1980-12-19 1982-06-25 Chinoin Gyogyszer Es Vegyeszet Suppositoires stables malgre un composant actif volatil et/ou decomposable et procede pour leur preparation
GB2126086A (en) * 1982-08-24 1984-03-21 Cilag Ag Medicated suppository containing gel-forming and gel-dispersing agents
GB2142238A (en) * 1983-07-01 1985-01-16 Nitto Electric Ind Co Pharmaceutical compositions for percutaneous administration
GB2142237A (en) * 1983-07-01 1985-01-16 Nitto Electric Ind Co Pharmaceutical compositions for percutaneous administration
FR2562798A1 (fr) * 1984-04-11 1985-10-18 Roehm Pharma Gmbh Agent pharmaceutique pour le traitement du psoriasis
FR2596991A1 (fr) * 1986-04-11 1987-10-16 Roehm Pharma Gmbh Medicament sous forme liquide pour le traitement du psoriasis, a base de polymeres filmogenes
EP0322197A1 (de) * 1987-12-22 1989-06-28 Drythanol Ltd. Dithranolzusammensetzungen
US5061486A (en) * 1987-12-22 1991-10-29 Drythanol Ltd. Dithranol composition containing no oily ingredients
FR2649608A1 (fr) * 1989-07-12 1991-01-18 Oreal Composition cosmetique sous forme d'un gel aqueux contenant en suspension des spheroides d'une substance lipidique solide non hydrophile
EP0412865A1 (de) * 1989-07-12 1991-02-13 L'oreal Wässeriges Gel, das Kügelchen aus einem festen nichthydrophilen Lipid suspendiert enthält
US5674504A (en) * 1989-07-12 1997-10-07 L'oreal Cosmetic composition in the form of an aqueous gel containing in suspension spheroids of a non-hydrophilic, lipoidal substance
EP1205218A1 (de) * 2000-11-14 2002-05-15 Benkert, Eugen Georg, Dr.med.dent. Topical-Antipsoriaticum mit Harnstoff, einem Corticoid und einem Desinfektionsmittel

Also Published As

Publication number Publication date
AU4813579A (en) 1979-12-20
AU521982B2 (en) 1982-05-13
IE48761B1 (en) 1985-05-15
DE2964135D1 (en) 1983-01-05
USRE32161E (en) 1986-05-27
CA1114744A (en) 1981-12-22
EP0006724B1 (de) 1982-12-01
JPS557272A (en) 1980-01-19
US4291062A (en) 1981-09-22
IE791172L (en) 1979-12-16

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